Three genes (Rfv-1, Rfv-2 and Rfv-3) have been identified which control host defense mechanisms required for spontaneous recovery from Friend virus-induced leukemia. Two of these genes (Rfv-1 and Rfv-2) are located in the major histocompatibility complex (H-2), and they affect the T lymphocyte response to virus-specific antigens. Rfv-2 appears to function as a dominant immune response gene. Rfv-1 acts by influencing the kinetics of development of the virus-specific T lymphocytes. Rfv-3 influences virus-specific humoral antibodies which are necessary but not sufficient for recovery. The actions of these antibodies in vivo have been studied using monoclonal antibodies derived from cells of mice recovering from leukemia.